Pharmacological Rationale for Targeting IL-17 in Asthma

Siti Farah Rahmawati; Maurice Te Velde; Huib A M Kerstjens; Alexander S S Dömling; Matthew Robert Groves; Reinoud Gosens

doi:10.3389/falgy.2021.694514

Pharmacological Rationale for Targeting IL-17 in Asthma

Front Allergy. 2021 Aug 30:2:694514. doi: 10.3389/falgy.2021.694514. eCollection 2021.

Authors

Siti Farah Rahmawati^{1

2

3}, Maurice Te Velde^{1

3}, Huib A M Kerstjens^{3

4}, Alexander S S Dömling⁵, Matthew Robert Groves⁵, Reinoud Gosens^{1

3}

Affiliations

¹ Department of Molecular Pharmacology, University of Groningen, Groningen, Netherlands.
² Department of Pharmacology and Clinical Pharmacy, Institut Teknologi Bandung, Bandung, Indonesia.
³ Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Centre Groningen (UMCG), Groningen, Netherlands.
⁴ Department of Pulmonary Medicine, University of Groningen and University Medical Center Groningen (UMCG), Groningen, Netherlands.
⁵ Department of Drug Design, University of Groningen, Groningen, Netherlands.

Abstract

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway.

Keywords: IL-17; airway remodeling; asthma; inflammation; pharmacology.

Publication types

Review